Manufacturing bespoke human organs; 3D printed nanocomposite trachea

制造定制人体器官；

• 批准号: EP/L020904/1
• 负责人: Alexander Seifalian
• 金额: $ 107.73万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL020904%2F1
• 关键词: Manufacturing; bespoke; human; organs; 3D

Organ failure and tissue loss are challenging health issues due to widespread aging population, injury, the lack of organs for transplantation and limitations of conventional artificial implants. There is a fast growing need in surgery to replace and repair soft tissues such as blood vessels, stent, trachea, skin, or even entire organs, such as bladder, kidney, heart, facial organs etc. The high demand for new artificial implants for long-term repair and substantially improved clinical outcome still remains .Our well-publicised successes in using tissue-engineering to replace hollow organs in cases of compassionate need have shown the world that an engineering approach to hollow organ replacement is feasible, as well as serving to highlight those areas where more work is required to provide bespoke manufactured tissue scaffolds for routine clinical use Being able to replicate a functional part of one's body as an exact match and therefore to be able to replace it 'as good as before' is familiar in science fiction. Most implants will share limitations that are associated with either the materials used or the traditional way in which they have been made. With the advancement of additive manufacturing technology, 3D printing, biomaterials and cell production, printing an artificial organs is becoming a science and engineering fact and understandably can save lives and enhance quality of life through surgical transplantation of such printed organs produced on-demand, specifically for the individual of interest. The project seeks to addresses the unmet need in traditional implants by exploiting our proprietary polymer nanocomposites developed at UCL and advanced digital additive manufacturing with surgical practice. we aim to develop a 3D advanced digital bio-printing system for polymer nanocomposites in order to manufacture a new-generation of synthetic soft organs 'on-demand' and bespoke to the patient's particular needs. Our extensive preclinical and on-going preclinical study on the nanocomposite-based organs will ensure the construct is able to induce angiogenesis and to perform function of an epithelium. Here we take these experiences in the compassionate case, and take trachea as an exemplar to develop a manufacturing method of producing bespoke tubular organs for transplantation with nanocomposite material. This proposal will allow us to develop; a) a customer made 3D bioprinter with multi-printing heads and an environmental chamber which can print 'live' soft organs/scaffolds with seeded cells to meet the individual patients needs; b) a series of polymer nanocomposites suitable for 3D printingorgan constructs/host scaffolds; c) a formulations of bio-inks for printing cells, proteins and biomolecules. d) a printed artificial tracheal constructs using their radiographic images with optimised biochemical, biophysical and mechanical properties. e) Establishment of in-vivo feasibility data through observation of restoration of respiratory function and normal tissue integration of pig models which will be surgically transplanted

器官衰竭和组织损失是具有挑战性的健康问题，由于广泛的人口老龄化，损伤，缺乏器官移植和传统的人工植入物的局限性。在外科手术中存在快速增长的需求，以替换和修复软组织，例如血管、支架、气管、皮肤，或甚至整个器官，例如膀胱、肾、心脏，面部器官等。对新型人工植入物的长期修复和显著改善临床效果的需求仍然很高。我们在使用组织-在有同情心需要的情况下，工程学上替换空心器官的方法已经向世界表明，工程学上替换空心器官的方法是可行的，以及用于突出需要更多工作以提供定制制造的组织支架用于常规临床用途的那些领域，能够复制一个人身体的功能部分作为一个精确的匹配，因此能够取代它“像以前一样好”是在科幻小说中熟悉的。大多数植入物都有与所用材料或传统制造方法相关的局限性。随着增材制造技术、3D打印、生物材料和细胞生产的进步，打印人造器官正在成为一个科学和工程事实，可以理解的是，通过按需生产的这种打印器官的手术移植，特别是针对感兴趣的个体，可以挽救生命并提高生活质量。该项目旨在通过利用我们在UCL开发的专有聚合物纳米复合材料和先进的数字增材制造与手术实践来解决传统植入物未满足的需求。我们的目标是为聚合物纳米复合材料开发一种先进的3D数字生物打印系统，以制造新一代的“按需”合成软器官，并根据患者的特殊需求定制。我们对基于纳米复合材料的器官进行的广泛的临床前和正在进行的临床前研究将确保该构建体能够诱导血管生成并执行上皮功能。在此，我们将这些经验，在同情的情况下，并以气管为例，开发一种制造方法，生产定制的管状器官移植与纳米复合材料。这项建议将使我们能够开发：a）客户定制的3D生物打印机，具有多打印头和环境室，可以打印“活的”软器官/支架，并接种细胞，以满足个体患者的需求; B）一系列适用于3D打印的聚合物纳米复合材料，包括生物芯片和生物芯片; c）用于打印细胞，蛋白质和生物分子的生物墨水配方。d）使用具有优化的生物化学、生物物理和机械性质的放射照相图像打印的人工气管构建体。e）通过观察将手术移植的猪模型的呼吸功能恢复和正常组织整合，建立体内可行性数据

项目成果

Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells.

• DOI: 10.1016/j.biomaterials.2018.09.013
• 发表时间: 2018-09
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Linxiao Wu;Adrián Magaz;Tao Wang;Chaozong Liu;A. Darbyshire;M. Loizidou;M. Emberton;M. Birchall-M.-Birchal

Elements of the niche for adult stem cell expansion.

成人干细胞扩张的小众元素。

• DOI: 10.1177/2041731417725464
• 发表时间: 2017-01
• 期刊: Journal of tissue engineering
• 影响因子: 8.2
• 作者: Redondo PA;Pavlou M;Loizidou M;Cheema U
• 通讯作者: Cheema U

3D Bioprinting of stimuli-responsive polymers synthesised from DE-ATRP into soft tissue replicas

• DOI: 10.1016/j.bprint.2018.02.002
• 发表时间: 2018-03
• 期刊: Bioprinting
• 作者: A. Aied;Wenhui Song;Wenxin Wang;Abdulrahman Baki;A. Sigen

Biomimetic heterogenous elastic tissue development.

• DOI: 10.1038/s41536-017-0021-4
• 发表时间: 2017
• 期刊: NPJ Regenerative medicine
• 影响因子: 7.2
• 作者: Tsai KJ;Dixon S;Hale LR;Darbyshire A;Martin D;de Mel A
• 通讯作者: de Mel A

Stiffness memory nanohybrid scaffolds generated by indirect 3D printing for biologically responsive soft implants.

• DOI: 10.1016/j.actbio.2018.09.016
• 发表时间: 2018-10
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Linxiao Wu;J. Virdee;E. Maughan;A. Darbyshire;G. Jell;M. Loizidou;M. Emberton;P. Butler;A. Howkins;A. Reynolds;I. Boyd;M. Birchall;Wenhui Song